Format

Send to

Choose Destination
Oncol Rep. 2012 May;27(5):1341-7. doi: 10.3892/or.2012.1677. Epub 2012 Feb 6.

Crotoxin enhances the antitumor activity of gefinitib (Iressa) in SK-MES-1 human lung squamous carcinoma cells.

Author information

1
Department of Cardiothoracic Surgery, the First Affiliated Hospital of Soochow University, and Department of Pharmacology, School of Pharmaceutical Science, Soochow University, Suzhou 215006, PR China.

Abstract

Crotoxin (CrTX), a neurotoxin, is isolated from the venom of South American rattlesnakes and has potent antitumor activity. Here, we investigated the antitumor effect of CrTX on the SK-MES-1 human lung squamous cell carcinoma cell line that has acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors. CrTX caused G1 arrest and p-JNK protein upregulation that resulted in apoptosis of SK-MES-1 cells. SP600125, a specific inhibitor of p-JNK, could rescue SK-MES-1 cells from CrTX-induced apoptosis. CrTX and gefinitib (Iressa) both inhibited the viability and proliferation of SK-MES-1 cells in a dose- and time-dependent manner. The combination of CrTX and Iressa significantly enhanced the antitumor activity of Iressa. In vivo studies revealed that CrTX caused increased damage to blood vessels and reduced tumor size when combined with Iressa. The present study showed that the JNK signal transduction pathway mediated the anti-apoptotic effect of CrTX, and furthermore, CrTX could enhance the antitumor effect of tyrosine kinase inhibitors in cells with acquired resistance.

PMID:
22322185
DOI:
10.3892/or.2012.1677
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Spandidos Publications
Loading ...
Support Center